Obesity is quickly becoming a global epidemic, which epidemic crosses all age and socio-economic groups. The number of overweight and obese people worldwide has risen from 857 million in 1980 to 2.1 billion in 2013 (Ng, et al., Global, Regional & National Prevalence of Overweight and Obesity in Children and Adults During 1980-2013: A Systematic Analysis for the Global Burden of Disease Study, Lancet (2014)). Additionally, obesity is known to be a major risk factor for the development of a number of diseases including Type 2 Diabetes or Type 2 diabetes mellitus (T2D).
The International Diabetes Federation estimates that approximately 380 million people worldwide have diabetes, up to 95% of which suffer from T2D. In T2D, the body fails to properly use insulin, or is insulin resistant. T2D is also generally characterized by hyperglycemia, insulin resistance and low insulin levels. T2D is thought to be primarily due to obesity and lack of exercise in people who are genetically predisposed.
Diet, exercise and weight control are the cornerstones of managing T2D. However, drug therapy may be required in which one or more drugs are used to control blood sugar levels. Current medications for treatment of T2D are oral medications including meglitinides, sulfonylureas, dipeptidyl-peptidase 4 (“DPP-4”) inhibitors, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, and sodium-glucose transporter 2 (“SGLT2”) inhibitors. Additionally, injectable medications, such as amylin mimetics and incretin mimetics are used to treat T2D.
A second type of diabetes mellitus, Type 1 (T1D), is a chronic condition in which little or no insulin is produced by the pancreas. Historically, T1D was treated with insulin administration in addition to the control of diet, exercise and weight. However, more recently treatment has included the transplantation of islets of Langerhans, which treatment suffers from a shortage of transplantable islets of Langerhans. Thus, even more recently, treatment development focused on developing sources of insulin-producing cells appropriate for engraftment. One such approach is the generation of insulin-producing cells from pluripotent stem cells, such as embryonic stem cells.
The production of enriched cultures of human embryonic stem cell-derived definitive endoderm and the further differentiation of such cells into pancreatic endocrine precursor cells is known (for example, US2009/0170198; Rezania, A. et al. Diabetes 2012; Rezania, A. et al. Stem Cells 2013; Bruin, J. E. et al. 2013; Bruin, J. E. et al. Stem Cell Research 2014). Published patent application, US2012/0039955, also describes a decrease in blood sugar in SCID mice with streptozotocin (STZ) induced T1D like state following transplantation of a population of encapsulated pancreatic endocrine precursor cells. It is also known that subsequent transplant of the pancreatic endocrine precursor cells into a body allows for still further differentiation into functional pancreatic endocrine cells.